Laryngeal EdemaCOMICNCT03372707
Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU
A study testing Cuff Leak Test in people with Laryngeal Edema, run by McMaster University at 3 sites in 3 countries.
Trial summary
Introduction: Endotracheal intubation and mechanical ventilation are lifesaving interventions that are commonly done in the intensive care unit (ICU). The act of intubating someone can cause laryngeal edema (LE) that, if extensive enough, can cause airway obstruction after a patient is extubated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Laryngeal Edema
- What is being tested?
- Cuff Leak Test
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 5 Jul 2018to 1 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible patients will be mechanically ventilated adults (>18 years) who are admitted to the ICU and an order to extubate has been provided by the treating physician.
Who cannot join
- A palliative care, a one-way extubation, or a decision to withdraw advances life support order has been written.
- Pregnancy.
- Patients at high risk for LE: burn patients, smoke inhalation injuries (as defined as singed facial hair or nasal hair, carbonaceous secretions/sputum, and known to be in an enclosed fire), blunt or penetrating trauma involving the neck and airway, postoperative head and neck surgeries, and patients admitted with airway edema to the ICU (e.g; anaphylaxis).
- Patients with either a difficult or traumatic endotracheal intubation.
- Patients receiving mechanical ventilation via tracheostomy.
- Known preexisting tracheolaryngeal abnormalities such as: vocal cord paralysis, tracheolaryngeal neoplasm, tracheomalacia, tracheolaryngeal stenosis, or previous head and neck surgeries.
Show all 11Show fewer
- Patients receiving systemic corticosteroids of greater than 30 mg of PO prednisone or equivalent, within 4 days prior to the decision to extubate.
- Patients who failed extubation attempt within the current ICU admission.
- History of postextubation airway obstruction.
- The ICU physician declined enrolling the patient.
- Patient had a failed CLT in the previous 24 hours.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Poland1 site
Jagiellonian University Medical College
Krakow, Lesser Poland Voivodeship, 31-066
Saudi Arabia1 site
Imam Adbulrahman Bin Faisal University
Dammam, Eastern Province, 34212
About this study
Official title: Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients Pilot Trial
Introduction: Endotracheal intubation and mechanical ventilation are lifesaving interventions that are commonly done in the intensive care unit (ICU). The act of intubating someone can cause laryngeal edema (LE) that, if extensive enough, can cause airway obstruction after a patient is extubated. To date, the only test that is available to predict this complication is the cuff leak test (CLT). However, its diagnostic accuracy is uncertain as there have been no randomized controlled trials (RCT) examining this. The Cuff leak and airway Obstruction in Mechanically ventilated ICU patients (COMIC) Randomized Control Trial will be done to examine the impact of CLT on postextubation stridor and reintubation. Subsequently, describing the diagnostic accuracy of this test.
Methods: This will be a multi-center centered, pragmatic, double blinded RCT. Mechanically ventilated patients in the ICU, who are deemed ready to be extubated will be included. All patients will have a CLT done prior to extubation. The results of the CLT in the intervention arm will be communicated to the treating physician, and decision to extubate will be left to the treating team, while the results of the CLT for patients in the control arm will not be communicated to the treating physician, and the patient will be extubated, regardless of the result of the CLT.
Objective: This is a pilot trial to assess feasibility of conducting a powered RCT. Feasibility outcomes include: consent rate, recruitment rate, and protocol adherence. Clinical outcomes will include postextubation stridor, reintubation, emergency surgical airway, ICU mortality, in hospital mortality, duration of mechanical ventilation, and ICU length of stay in days.
Read the detailed description
INTRODUCTION Endotracheal intubation and mechanical ventilation are lifesaving interventions. However, as with acute interventions, can be associated with serious complications. One such complication is laryngeal edema (LE) that occurs in 4-55% of patients. LE is thought to be caused by marked polymorphonuclear infiltration to the traumatized upper airway postintubation. The incidence of LE increases as the duration of intubation accrues, but it can occur as early as the first 24 hours of intubation. LE can result in airway narrowing and increased airflow velocity. It is postulated that narrowing of the lumen by 50% or more may result in postextubation stridor and respiratory distress. As a result, 3.5% (range 0-10.5%) of patients with LE will fail an extubation attempt and require reintubation. For various reasons, reintubation has a significant morbidity and mortality.
Identifying patients with LE can be challenging, the presence of the endotracheal tube (ETT) precludes direct visualization of the upper airway prior to extubation, therefore, clinicians cannot accurately predict airway obstruction before it occurs. A cuff-leak test (CLT) was first described in 1988 as a surrogate for direct visualization and a screening for airway edema prior to extubation. This test involves deflating the balloon cuff on an ETT and observing if the patient is able to breathe around it. If air can pass around the ETT, it suggest that the airway is patent and clinicians may proceed with extubation. A small leak or complete absence of one, would suggest an airway obstruction.
There are conflicting results on the utility and accuracy of a CLT. To date, two meta-analyses of observational studies examined the diagnostic accuracy of a CLT. One meta-analysis reports that a failed CLT is insensitive but a specific predictor of LE (pooled sensitivity and specificity 0.56; 95% CI, 0.48-0.63 and 0.92; 95% CI, 0.90-0.93, respectively) and reintubation (pooled sensitivity and specificity for reintubation 0.63; 95% CI, 0.38-0.84 and 0.86; 95% CI, 0.81-0.90, respectively). While the second meta-analysis also states that the failed CLT was associated with postextubation LE, particularly in patients with > 5 days duration of intubation (odds ratio [OR]=2.09; 95% CI, 1.28-2.89), it was not associated with higher odds of reintubation (OR=0.94; 95% CI, 0.32-1.57).
Despite the lack of high quality studies, an absent cuff leak usually results in delayed extubation and exposure to corticosteroids to empirically treat airway edema. A recent meta-analysis of 11 parallel randomized controlled trails (RCTs) with a total of 2472 patients examined the effect of prophylactic corticosteroids prior to extubation on postextubation stridor and reintubation. Prophylactic corticosteroids use reduced the risk of postextubation airway events when compared to placebo or no treatment (RR 0.43; 95% CI 0.29-0.66, P=0.002). A subgroup analysis demonstrates that this benefit is only significant in patients that are deemed "high risk" for LE. Prophylactically treating unspecified patients shows no reduction in postextubation events and exposes patients to high dose steroids (16). Moreover, a false positive CLT can unnecessarily delay extubation, leading to a prolonged length of stay in the intensive care unit (ICU), barotraumas, and increased risk of ventilator associated pneumonias, therefore, exposing patients unnecessarily to these undesirable outcomes. On the other hand, if a CLT is not performed, or if in case of a false negative test, some patients may fail the extubation attempt and require reintubation.
Recent clinical practice guidelines for using CLT reflect this uncertainty. The American Thoracic Society guidelines on liberation of mechanical ventilation issued a weak recommendation for performing CLT in mechanically ventilated adults who are at high risk for postextubation stridor (conditional recommendation, very low certainty). There is also significant clinical equipoise. A recent unpublished survey found that 42% (12/26) of Canadian intensive care unit (ICU) physicians either never or rarely request to know the results of a cuff leak test prior to extubating a patient that is at moderate risk of laryngeal edema while 23% will always or usually order the test. Therefore, a large RCT is necessary to investigate the diagnostic accuracy of the CLT and its impact on patients' outcomes.
Herein, the investigators are reporting the protocol for the COMIC Pilot Trial. The COMIC (Cuff leak and airway Obstruction in Mechanically ventilated ICU patients) pilot trial will be a multicenter, randomized, concealed, blinded, parallel-group, pragmatic pilot trial. The purpose is to determine the feasibility of undertaking a powered RCT to examine the impact of CLT on postextubation stridor and reintubation. Subsequently, describing the diagnostic accuracy of this test.
- Conditions
- Laryngeal Edema
- Being tested
- Cuff Leak Test
- Keywords
- Cuff leak test, Post-extubation airway obstruction, Laryngeal edema
- Medical subject headings
- Laryngeal Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cuff Leak TestDiagnostic test
The Respiratory Therapist (RT) will perform the CLT on all enrolled patients. The patients will first be switched to volume assist-control (V-AC) with a respiratory rate of 10 breaths/min (to allow patient assist), constant flow of 60 l/min, and tidal volume set to match the average tidal volume currently being delivered during supportive ventilation. The RT will document the average exhaled volume over 3-5 breaths after switching to V-AC. The test will be performed by deflating the ETT balloon cuff with a 10 cc syringe, and: a) auscultation with a stethoscope to identify audible air leak around the ETT, and b) measuring the difference between the average exhaled volume prior to cuff deflation and the average exhaled volume over 3-5 breaths after cuff deflation.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm | Experimental | Patients randomized to the intervention arm will have the results of the Cuff Leak Test (CLT) (whether failed or passed) communicated to the treating physician; the treating physician will decide whether to proceed with extubation or not based on the CLT results. It is at the discretion of the treating physician to provide corticosteroids (4-5 mg of intravenous dexamethasone every six hours for up to 24 hours, with the last dose given one hour preceding extubation) and/or delay extubation by 24 hours should the patient fail the CLT. Receives: Diagnostic Test: Cuff Leak Test |
| Control Arm | No intervention | In the control arm of this trial; the treating physicians and healthcare workers will be blinded to the results of the Cuff Leak Test (CLT); therefore, the Respiratory Therapist (RT) will proceed with extubation without delay or administering systemic steroid, regardless to the CLT results. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Consent Rate
A successful consent rate will be defined as 70% of substitute decision makers (SDMs) or patients approached to consent, choosing to participate in the trial. This will be calculated as the overall proportion of SDMs or patients consenting out of those approached (with 95% CI). Note that a mixed consent model will be obtained. In Canada and Saudi Arabia, a priori or deferred consent model will be used. In Poland, a waved consent model will be used.
Measured: 1 year
Recruitment Rate
A successful recruitment rate will be defined as achieving enrollment of 40 patients, conventionally expressed as four patients per month over the duration of the trial. While the pilot trial is ongoing, recruitment will be reviewed weekly and the screening records will be reviewed monthly with the cases of missed eligible patients reviewed. If applicable, barriers to enrollment will be addressed to maximize recruitment. The recruitment metric will be measured and interpreted at the end of the pilot trial by calculating the mean number of recruited patients per active screening month.
Measured: 1 year
Protocol Adherence
Successful adherence will be defined as ≥80%. The adherence will be calculated as the proportion of patients that were assigned to the control arm being extubated after CLT being performed and the portion of people that assigned to the intervention arm who are given the prescribed steroids for a failed CLT. As this pilot trial is ongoing, investigators will review adherence monthly and investigate the reasons for compliance failure. All reasons for either failure to extubate after a failed CLT in the control arm will be investigated. The RC will review the Respiratory Therapists' notes, and the medication profile to determine actual compliance. All reasons for non-compliance will be recorded for both groups using distinguishing clinical reasons (eg. Palliation, death, consent withdrawal, errors).
Measured: 1 year
Secondary outcomes (8)
Postextubation stridor
Defined as an audible high pitched inspiratory noise caused by turbulent airflow through the narrowed airway that is detectable with or without a stethoscope within 48 hours of extubation.
Measured: 48 hours after original extubation
Clinically significant postextubation stridor
Defined as stridor (see definition above) that requires medical intervention such as the administration of systemic steroids, racemic epinephrine, or Heli-ox.
Measured: 48 hours after original extubation
Reintubation
Defined as reintubation within 72 hours of original extubation while in the ICU.
Measured: 72 hours after original extubation
Emergency surgical airway
Defined as performing urgent tracheotomy or cricothyroidotomy for a life-threatening airway obstruction
Measured: 30 days
In ICU mortality
Measured: 1 year
In hospital mortality truncated at 30 days
Measured: 30 days
Duration of mechanical ventilation
Defined as time on the ventilator after randomization in days.
Measured: 1 year
ICU length of stay in days
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2017
- Study start5 Jul 2018
- Primary completion1 May 2019
- Study completion1 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Laryngeal EdemaStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kimberley A Lewis, MD, Principal investigator, McMaster UniversityWaleed Alhazzani, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03372707
- Sponsor's protocol ID
- 20170701
- Acronym
- COMIC
- Status last verified
- Aug 2022
- First submitted
- 1 Dec 2017
- Last updated
- 26 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maury E, Guglielminotti J, Alzieu M, Qureshi T, Guidet B, Offenstadt G. How to identify patients with no risk for postextubation stridor? J Crit Care. 2004 Mar;19(1):23-8. doi: 10.1016/j.jcrc.2004.02.005.
PubMed 15101002Tadie JM, Behm E, Lecuyer L, Benhmamed R, Hans S, Brasnu D, Diehl JL, Fagon JY, Guerot E. Post-intubation laryngeal injuries and extubation failure: a fiberoptic endoscopic study. Intensive Care Med. 2010 Jun;36(6):991-8. doi: 10.1007/s00134-010-1847-z. Epub 2010 Mar 18.
PubMed 20237758Sutherasan Y, Theerawit P, Hongphanut T, Kiatboonsri C, Kiatboonsri S. Predicting laryngeal edema in intubated patients by portable intensive care unit ultrasound. J Crit Care. 2013 Oct;28(5):675-80. doi: 10.1016/j.jcrc.2013.05.011. Epub 2013 Jun 24.
PubMed 23806246Francois B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T, Brenet O, Preux PM, Vignon P; Association des Reanimateurs du Centre-Ouest (ARCO). 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial. Lancet. 2007 Mar 31;369(9567):1083-9. doi: 10.1016/S0140-6736(07)60526-1.
PubMed 17398307Zhou T, Zhang HP, Chen WW, Xiong ZY, Fan T, Fu JJ, Wang L, Wang G. Cuff-leak test for predicting postextubation airway complications: a systematic review. J Evid Based Med. 2011 Nov;4(4):242-54. doi: 10.1111/j.1756-5391.2011.01160.x.
PubMed 23672755Way WL, Sooy FA. Histologic changes produced by endotracheal intubation. Ann Otol Rhinol Laryngol. 1965 Sep;74(3):799-812. doi: 10.1177/000348946507400318. No abstract available.
PubMed 4954421Mackle T, Meaney J, Timon C. Tracheoesophageal compression associated with substernal goitre. Correlation of symptoms with cross-sectional imaging findings. J Laryngol Otol. 2007 Apr;121(4):358-61. doi: 10.1017/S0022215106004142. Epub 2006 Oct 26.
PubMed 17064460Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med. 1998 Aug;158(2):489-93. doi: 10.1164/ajrccm.158.2.9711045.
PubMed 9700126Demling RH, Read T, Lind LJ, Flanagan HL. Incidence and morbidity of extubation failure in surgical intensive care patients. Crit Care Med. 1988 Jun;16(6):573-7. doi: 10.1097/00003246-198806000-00001.
PubMed 3371019Esteban A, Alia I, Gordo F, Fernandez R, Solsona JF, Vallverdu I, Macias S, Allegue JM, Blanco J, Carriedo D, Leon M, de la Cal MA, Taboada F, Gonzalez de Velasco J, Palazon E, Carrizosa F, Tomas R, Suarez J, Goldwasser RS. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):459-65. doi: 10.1164/ajrccm.156.2.9610109.
PubMed 9279224Frutos-Vivar F, Esteban A, Apezteguia C, Gonzalez M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, Perez F, Penuelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011 Oct;26(5):502-509. doi: 10.1016/j.jcrc.2010.12.015. Epub 2011 Mar 3.
PubMed 21376523Torres A, Gatell JM, Aznar E, el-Ebiary M, Puig de la Bellacasa J, Gonzalez J, Ferrer M, Rodriguez-Roisin R. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995 Jul;152(1):137-41. doi: 10.1164/ajrccm.152.1.7599812.
PubMed 7599812Seymour CW, Martinez A, Christie JD, Fuchs BD. The outcome of extubation failure in a community hospital intensive care unit: a cohort study. Crit Care. 2004 Oct;8(5):R322-7. doi: 10.1186/cc2913. Epub 2004 Jul 20.
PubMed 15469575Potgieter PD, Hammond JM. "Cuff" test for safe extubation following laryngeal edema. Crit Care Med. 1988 Aug;16(8):818. doi: 10.1097/00003246-198808000-00020. No abstract available.
PubMed 3396380Ochoa ME, Marin Mdel C, Frutos-Vivar F, Gordo F, Latour-Perez J, Calvo E, Esteban A. Cuff-leak test for the diagnosis of upper airway obstruction in adults: a systematic review and meta-analysis. Intensive Care Med. 2009 Jul;35(7):1171-9. doi: 10.1007/s00134-009-1501-9. Epub 2009 Apr 28.
PubMed 19399474
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients Pilot Trial
- ClinicalTrials.gov ID
- NCT03372707
- Acronym / sponsor ID
- COMIC / 20170701
- Conditions
- Laryngeal Edema
- Keywords
- Cuff leak test, Post-extubation airway obstruction, Laryngeal edema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 5 Jul 2018 (actual)
- Primary completion
- 1 May 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 14 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: Endotracheal intubation and mechanical ventilation are lifesaving interventions that are commonly done in the intensive care unit (ICU). The act of intubating someone can cause laryngeal edema (LE) that, if extensive enough, can cause airway obstruction after a patient is extubated. To date, the only test that is available to predict this complication is the cuff leak test (CLT). However, its diagnostic accuracy is uncertain as there have been no randomized controlled trials (RCT) examining this. The Cuff leak and airway Obstruction in Mechanically ventilated ICU patients (COMIC) Randomized Control Trial will be done to examine the impact of CLT on postextubation stridor and reintubation. Subsequently, describing the diagnostic accuracy of this test.
Methods: This will be a multi-center centered, pragmatic, double blinded RCT. Mechanically ventilated patients in the ICU, who are deemed ready to be extubated will be included. All patients will have a CLT done prior to extubation. The results of the CLT in the intervention arm will be communicated to the treating physician, and decision to extubate will be left to the treating team, while the results of the CLT for patients in the control arm will not be communicated to the treating physician, and the patient will be extubated, regardless of the result of the CLT.
Objective: This is a pilot trial to assess feasibility of conducting a powered RCT. Feasibility outcomes include: consent rate, recruitment rate, and protocol adherence. Clinical outcomes will include postextubation stridor, reintubation, emergency surgical airway, ICU mortality, in hospital mortality, duration of mechanical ventilation, and ICU length of stay in days.
Detailed description
INTRODUCTION Endotracheal intubation and mechanical ventilation are lifesaving interventions. However, as with acute interventions, can be associated with serious complications. One such complication is laryngeal edema (LE) that occurs in 4-55% of patients. LE is thought to be caused by marked polymorphonuclear infiltration to the traumatized upper airway postintubation. The incidence of LE increases as the duration of intubation accrues, but it can occur as early as the first 24 hours of intubation. LE can result in airway narrowing and increased airflow velocity. It is postulated that narrowing of the lumen by 50% or more may result in postextubation stridor and respiratory distress. As a result, 3.5% (range 0-10.5%) of patients with LE will fail an extubation attempt and require reintubation. For various reasons, reintubation has a significant morbidity and mortality.
Identifying patients with LE can be challenging, the presence of the endotracheal tube (ETT) precludes direct visualization of the upper airway prior to extubation, therefore, clinicians cannot accurately predict airway obstruction before it occurs. A cuff-leak test (CLT) was first described in 1988 as a surrogate for direct visualization and a screening for airway edema prior to extubation. This test involves deflating the balloon cuff on an ETT and observing if the patient is able to breathe around it. If air can pass around the ETT, it suggest that the airway is patent and clinicians may proceed with extubation. A small leak or complete absence of one, would suggest an airway obstruction.
There are conflicting results on the utility and accuracy of a CLT. To date, two meta-analyses of observational studies examined the diagnostic accuracy of a CLT. One meta-analysis reports that a failed CLT is insensitive but a specific predictor of LE (pooled sensitivity and specificity 0.56; 95% CI, 0.48-0.63 and 0.92; 95% CI, 0.90-0.93, respectively) and reintubation (pooled sensitivity and specificity for reintubation 0.63; 95% CI, 0.38-0.84 and 0.86; 95% CI, 0.81-0.90, respectively). While the second meta-analysis also states that the failed CLT was associated with postextubation LE, particularly in patients with > 5 days duration of intubation (odds ratio [OR]=2.09; 95% CI, 1.28-2.89), it was not associated with higher odds of reintubation (OR=0.94; 95% CI, 0.32-1.57).
Despite the lack of high quality studies, an absent cuff leak usually results in delayed extubation and exposure to corticosteroids to empirically treat airway edema. A recent meta-analysis of 11 parallel randomized controlled trails (RCTs) with a total of 2472 patients examined the effect of prophylactic corticosteroids prior to extubation on postextubation stridor and reintubation. Prophylactic corticosteroids use reduced the risk of postextubation airway events when compared to placebo or no treatment (RR 0.43; 95% CI 0.29-0.66, P=0.002). A subgroup analysis demonstrates that this benefit is only significant in patients that are deemed "high risk" for LE. Prophylactically treating unspecified patients shows no reduction in postextubation events and exposes patients to high dose steroids (16). Moreover, a false positive CLT can unnecessarily delay extubation, leading to a prolonged length of stay in the intensive care unit (ICU), barotraumas, and increased risk of ventilator associated pneumonias, therefore, exposing patients unnecessarily to these undesirable outcomes. On the other hand, if a CLT is not performed, or if in case of a false negative test, some patients may fail the extubation attempt and require reintubation.
Recent clinical practice guidelines for using CLT reflect this uncertainty. The American Thoracic Society guidelines on liberation of mechanical ventilation issued a weak recommendation for performing CLT in mechanically ventilated adults who are at high risk for postextubation stridor (conditional recommendation, very low certainty). There is also significant clinical equipoise. A recent unpublished survey found that 42% (12/26) of Canadian intensive care unit (ICU) physicians either never or rarely request to know the results of a cuff leak test prior to extubating a patient that is at moderate risk of laryngeal edema while 23% will always or usually order the test. Therefore, a large RCT is necessary to investigate the diagnostic accuracy of the CLT and its impact on patients' outcomes.
Herein, the investigators are reporting the protocol for the COMIC Pilot Trial. The COMIC (Cuff leak and airway Obstruction in Mechanically ventilated ICU patients) pilot trial will be a multicenter, randomized, concealed, blinded, parallel-group, pragmatic pilot trial. The purpose is to determine the feasibility of undertaking a powered RCT to examine the impact of CLT on postextubation stridor and reintubation. Subsequently, describing the diagnostic accuracy of this test.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm | Experimental | Diagnostic Test: Cuff Leak TestPatients randomized to the intervention arm will have the results of the Cuff Leak Test (CLT) (whether failed or passed) communicated to the treating physician; the treating physician will decide whether to proceed with extubation or not based on the CLT results. It is at the discretion of the treating physician to provide corticosteroids (4-5 mg of intravenous dexamethasone every six hours for up to 24 hours, with the last dose given one hour preceding extubation) and/or delay extubation by 24 hours should the patient fail the CLT. |
| Control Arm | No intervention | –In the control arm of this trial; the treating physicians and healthcare workers will be blinded to the results of the Cuff Leak Test (CLT); therefore, the Respiratory Therapist (RT) will proceed with extubation without delay or administering systemic steroid, regardless to the CLT results. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Eligible patients will be mechanically ventilated adults (>18 years) who are admitted to the ICU and an order to extubate has been provided by the treating physician.
Key exclusion criteria (11 listed)
- A palliative care, a one-way extubation, or a decision to withdraw advances life support order has been written.
- Pregnancy.
- Patients at high risk for LE: burn patients, smoke inhalation injuries (as defined as singed facial hair or nasal hair, carbonaceous secretions/sputum, and known to be in an enclosed fire), blunt or penetrating trauma involving the neck and airway, postoperative head and neck surgeries, and patients admitted with airway edema to the ICU (e.g; anaphylaxis).
- Patients with either a difficult or traumatic endotracheal intubation.
- Patients receiving mechanical ventilation via tracheostomy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cuff Leak TestThe Respiratory Therapist (RT) will perform the CLT on all enrolled patients. The patients will first be switched to volume assist-control (V-AC) with a respiratory rate of 10 breaths/min (to allow patient assist), constant flow of 60 l/min, and tidal volume set to match the average tidal volume currently being delivered during supportive ventilation. The RT will document the average exhaled volume over 3-5 breaths after switching to V-AC. The test will be performed by deflating the ETT balloon cuff with a 10 cc syringe, and: a) auscultation with a stethoscope to identify audible air leak around the ETT, and b) measuring the difference between the average exhaled volume prior to cuff deflation and the average exhaled volume over 3-5 breaths after cuff deflation. | Diagnostic test | Intervention Arm |
Primary outcome
Consent Rate
Time frame: 1 year
A successful consent rate will be defined as 70% of substitute decision makers (SDMs) or patients approached to consent, choosing to participate in the trial. This will be calculated as the overall proportion of SDMs or patients consenting out of those approached (with 95% CI). Note that a mixed consent model will be obtained. In Canada and Saudi Arabia, a priori or deferred consent model will be used. In Poland, a waved consent model will be used.
Recruitment Rate
Time frame: 1 year
A successful recruitment rate will be defined as achieving enrollment of 40 patients, conventionally expressed as four patients per month over the duration of the trial. While the pilot trial is ongoing, recruitment will be reviewed weekly and the screening records will be reviewed monthly with the cases of missed eligible patients reviewed. If applicable, barriers to enrollment will be addressed to maximize recruitment. The recruitment metric will be measured and interpreted at the end of the pilot trial by calculating the mean number of recruited patients per active screening month.
Protocol Adherence
Time frame: 1 year
Successful adherence will be defined as ≥80%. The adherence will be calculated as the proportion of patients that were assigned to the control arm being extubated after CLT being performed and the portion of people that assigned to the intervention arm who are given the prescribed steroids for a failed CLT. As this pilot trial is ongoing, investigators will review adherence monthly and investigate the reasons for compliance failure. All reasons for either failure to extubate after a failed CLT in the control arm will be investigated. The RC will review the Respiratory Therapists' notes, and the medication profile to determine actual compliance. All reasons for non-compliance will be recorded for both groups using distinguishing clinical reasons (eg. Palliation, death, consent withdrawal, errors).
8 secondary outcomes
Postextubation stridor
Time frame: 48 hours after original extubation
Clinically significant postextubation stridor
Time frame: 48 hours after original extubation
Reintubation
Time frame: 72 hours after original extubation
Emergency surgical airway
Time frame: 30 days
In ICU mortality
Time frame: 1 year
In hospital mortality truncated at 30 days
Time frame: 30 days
Duration of mechanical ventilation
Time frame: 1 year
ICU length of stay in days
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2022.
- Background: PubMed 15101002Maury E, Guglielminotti J, Alzieu M, Qureshi T, Guidet B, Offenstadt G. How to identify patients with no risk for postextubation stridor? J Crit Care. 2004 Mar;19(1):23-8. doi: 10.1016/j.jcrc.2004.02.005.
- Background: PubMed 20237758Tadie JM, Behm E, Lecuyer L, Benhmamed R, Hans S, Brasnu D, Diehl JL, Fagon JY, Guerot E. Post-intubation laryngeal injuries and extubation failure: a fiberoptic endoscopic study. Intensive Care Med. 2010 Jun;36(6):991-8. doi: 10.1007/s00134-010-1847-z. Epub 2010 Mar 18.
- Background: PubMed 23806246Sutherasan Y, Theerawit P, Hongphanut T, Kiatboonsri C, Kiatboonsri S. Predicting laryngeal edema in intubated patients by portable intensive care unit ultrasound. J Crit Care. 2013 Oct;28(5):675-80. doi: 10.1016/j.jcrc.2013.05.011. Epub 2013 Jun 24.
- Background: PubMed 17398307Francois B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T, Brenet O, Preux PM, Vignon P; Association des Reanimateurs du Centre-Ouest (ARCO). 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial. Lancet. 2007 Mar 31;369(9567):1083-9. doi: 10.1016/S0140-6736(07)60526-1.
- Background: PubMed 23672755Zhou T, Zhang HP, Chen WW, Xiong ZY, Fan T, Fu JJ, Wang L, Wang G. Cuff-leak test for predicting postextubation airway complications: a systematic review. J Evid Based Med. 2011 Nov;4(4):242-54. doi: 10.1111/j.1756-5391.2011.01160.x.
- Background: PubMed 4954421Way WL, Sooy FA. Histologic changes produced by endotracheal intubation. Ann Otol Rhinol Laryngol. 1965 Sep;74(3):799-812. doi: 10.1177/000348946507400318. No abstract available.
- Background: PubMed 17064460Mackle T, Meaney J, Timon C. Tracheoesophageal compression associated with substernal goitre. Correlation of symptoms with cross-sectional imaging findings. J Laryngol Otol. 2007 Apr;121(4):358-61. doi: 10.1017/S0022215106004142. Epub 2006 Oct 26.
- Background: PubMed 9700126Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med. 1998 Aug;158(2):489-93. doi: 10.1164/ajrccm.158.2.9711045.
- Background: PubMed 3371019Demling RH, Read T, Lind LJ, Flanagan HL. Incidence and morbidity of extubation failure in surgical intensive care patients. Crit Care Med. 1988 Jun;16(6):573-7. doi: 10.1097/00003246-198806000-00001.
- Background: PubMed 9279224Esteban A, Alia I, Gordo F, Fernandez R, Solsona JF, Vallverdu I, Macias S, Allegue JM, Blanco J, Carriedo D, Leon M, de la Cal MA, Taboada F, Gonzalez de Velasco J, Palazon E, Carrizosa F, Tomas R, Suarez J, Goldwasser RS. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):459-65. doi: 10.1164/ajrccm.156.2.9610109.
- Background: PubMed 21376523Frutos-Vivar F, Esteban A, Apezteguia C, Gonzalez M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, Perez F, Penuelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011 Oct;26(5):502-509. doi: 10.1016/j.jcrc.2010.12.015. Epub 2011 Mar 3.
- Background: PubMed 7599812Torres A, Gatell JM, Aznar E, el-Ebiary M, Puig de la Bellacasa J, Gonzalez J, Ferrer M, Rodriguez-Roisin R. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995 Jul;152(1):137-41. doi: 10.1164/ajrccm.152.1.7599812.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kimberley A Lewis, MD principal investigator
McMaster University
Waleed Alhazzani, MD principal investigator
McMaster University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cuff Leak Test in people with Laryngeal Edema, run by McMaster University at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada, Poland, Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Consent Rate (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03372707, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2022.